Publications

Joint models for longitudinal and event-time data can be used to understand the co-development of multiple correlated non-fatal outcomes, such as those encountered when studying diabetic microvascular complications. However, such models were not developed for event-times characterized by a multistate process where the entry time into certain states is interval-censored, which is an important feature of interval cohort study designs. Our aim was to develop a joint model for this setting....

Researchers are increasingly interested in identifying different parts of the genome which work together to influence a phenotypic trait. A major objective in bioinformatics involves finding groups of variables determined from omics technologies such as DNA methylation sites, transcriptome profiling, etc. Given one set of variables, one could determine how variables within work together to influence an outcome. These groups of variables are called functional modules and previous work has...

Many patients with chronic myeloid leukemia (CML) treated with adenosine triphosphate (ATP)-competitive tyrosine kinase inhibitors (TKIs) experience persistent adverse events (AEs) that negatively impact daily living and the ability to remain on treatment. Asciminib, an allosteric inhibitor of BCR::ABL1, was designed to enhance efficacy and reduce off-target effects vs ATPcompetitive TKIs. The phase 3 randomized ASC4FIRST trial established the overall favorable safety profile of asciminib in...

Osmotic stressors impair tissue expansion and slow crop development, which can ultimately reduce yield. The mechanisms through which dividing and differentiating cells perceive, integrate, and respond to stress are not well understood. To explore this knowledge gap, we assessed Asian rice (Oryza sativa) seedling responses to drought and salinity stress by performing single-nucleus transcriptome analyses on developing leaves and by assaying ion distribution using ICP-MS and CoroNa Green staining....

Relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) remains a leading cause of cancer-related death in children and young adults. While CD19-directed chimeric antigen receptor T cell (CAR-T) therapy offers promise, high rates of long-term failure underscore the need to understand resistance mechanisms. Our studies found p53 inactivation promotes CAR-T resistance in human pre-B-ALL cell lines. Through genome-wide CRISPR/Cas9 screening of CAR-sensitive TP53-wildtype and CAR-resistant...

Accurate representation of plant photosynthesis in terrestrial biosphere models (TBMs) is critical for reliable carbon-cycle simulations. Most TBMs employ the Farquhar-von Caemmerer-Berry (FvCB) model, which uses an empirical representation of electron transport that limits the simulation of gross primary productivity (GPP) and solar-induced chlorophyll fluorescence (SIF) under variable conditions. Here, we present BEPS-CB6F, an improved model that incorporates the mechanistic cytochrome b(6)f...

To advance the computational simulation of cellular life, we propose a virtual yeast, an artificial intelligence (AI)-driven agent that models eukaryotic cellular behaviours by integrating multimodal biological data, mechanistic reasoning and active experimentation using Saccharomyces cerevisiae as a genetically tractable and data-rich model system. Cellular complexity is decomposed into eight function-centred modules, spanning genetic, metabolic and structural systems, each realized as a...

CONCLUSIONS: The framework facilitates benchmarking and expert assessment of AI-driven auto-segmentation tools, addressing the need for transparency and reproducibility in this domain. Through its emphasis on clinical acceptability, our framework fosters the integration of AI models into clinical environments, specifically within radiation therapy.

Undifferentiated pleomorphic sarcoma (UPS) is one of the most common adult soft tissue sarcomas (STS), yet therapeutic progress remains limited due to the absence of recurrent oncogenic driver mutations. To identify tumor suppressors contributing to UPS pathogenesis, we performed a customized in vivo CRISPR/Cas9 screen in mice. This approach identified BRCA1-associated protein 1 (BAP1) as a potent tumor suppressor in STS. Integrative analyses using RNA sequencing, multiplex immunohistochemistry,...

Family physicians are well-positioned to support both persons living with dementia (PLWD) and their caregivers. However, current electronic medical record (EMR) systems do not capture the relational and interdependent nature of dementia care. Dyadic data, linking the records of persons living with dementia (PLWD) and their caregivers, could support more integrated, proactive, and personalized care. While there is growing interest in leveraging EMRs for this purpose, few systems enable routine...

CONCLUSIONS: The implementation of Interact-North represents a scalable model to address the gap in psychosocial support for families, but funding remains a barrier.

Lysine demethylase 2A (KDM2A) is a key epigenetic regulator and promising target for inhibition since its loss is selectively lethal in cancers reliant on Alternative Lengthening of Telomeres (ALT). Here we investigated the mechanism of compound 183c, a potent KDM2A inhibitor described in the patent literature. Biophysical studies showed that 183c requires the co-factor 2-oxoglutarate (2OG) for binding. A 2.2 Å crystal structure of the KDM2A-183c-2OG ternary complex explained the selectivity of...

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Temperate inland wetlands have long been viewed as climate regulators, with sustained CO₂ sequestration offsetting continuous CH₄ emissions over centennial-millennial timescales. However, the net climatic effect of these opposing fluxes remains uncertain under anthropogenic warming as they differ in both magnitude and atmospheric lifetime. We combine 19,000 CH₄ chamber measurements from 202 temperate inland wetlands with carbon burial rates from 16 dated sediment cores in North America's Prairie...

CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumour detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and inter-radiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence...

The liver is composed of diverse cell populations that coordinate essential metabolic and immune functions. Single-cell transcriptomics has advanced characterization of liver cellular composition, but dissociation of tissue to single-cells can introduce biases through the enrichment or depletion of cell types. Spatial transcriptomics is a complementary approach to avoid inherent bias for cell populations and to add important spatial context. The Visium HD spatial transcriptomics technology from...

Ensuring defensible policy inferences and robust decision reliability is fundamental for multi-criteria decision-making activities, particularly in transport safety engineering. This study developed a hybrid preference function-nested and machine learning-embedded decision model, i.e., EXPROM II-K-means with a linear discriminant analysis, to provide a robust support system for policy setting and decision making. The proposed model incorporates a refined nonparametric preference function into...

The rules of prokaryotic cell design remain elusive. Here, a theory is presented for interpreting growth rate, overflow metabolism, respiration efficiency, and maintenance energy flux based on cell dimensions, membrane protein crowding, and metabolism. The theory employs biophysical properties and systems analysis to successfully interpret phenotypes of Escherichia coli K-12 strains MG1655 and NCM3722. These strains are genetically similar but differ in surface area-to-volume (SA : V) ratios (~...

Epithelial cancers such as stomach and ovarian cancer tend to metastasize to the peritoneum, often leading to intractable disease and poor survival. The mechanisms that enable gastric cancer cells to implant, invade, and survive in the peritoneal niche are poorly understood. We developed a novel human peritoneal explant model using freshly harvested peritoneal tissue samples. GFP-labeled human gastric adenocarcinoma cells (AGS) were co-cultured with the peritoneal samples, and 2% of these cells...

Single-cell RNA sequencing has advanced our understanding of cellular heterogeneity. Ensuring the replicability of identified cell clusters across studies is essential for determining their biological robustness. We assess the replicability of cell clusters identified in two large mouse brain atlases, one generated using single-cell RNA sequencing and the other with single nuclei. Both profile over 4 million cells and group them into over 5,000 clusters. Using transcriptome-wide neighbor voting,...